JP2017529067A5 - - Google Patents

Claims (16)

An antigen binding protein comprising at least one CD3 binding site, wherein said CD3 binding site comprises:
(A) the variable heavy chain domain (VH) shown in SEQ ID NO: 8 and the variable light chain domain (VL) shown in SEQ ID NO: 3, or
(B) the variable heavy chain domain (VH) shown in SEQ ID NO: 9 and the variable light chain domain (VL) shown in SEQ ID NO: 4, or
(C) the variable heavy chain domain (VH) shown in SEQ ID NO: 7 and the variable light chain domain (VL) shown in SEQ ID NO: 2, or
(D) the variable heavy chain domain (VH) shown in SEQ ID NO: 6 and the variable light chain domain (VL) shown in SEQ ID NO: 1, or
( E ) a variable heavy chain domain (VH) having at least 95% sequence identity to said VH set forth in SEQ ID NO: 8, wherein the amino acid residue at position 111 is Y or H; and A variable light chain domain (VL) having at least 95% sequence identity to said VL as shown in ID No. 3, wherein the amino acid residue at position 49 is G or A, or
( F ) a variable heavy chain domain (VH) comprising 1 to 5 conservative amino acid substitutions relative to said VH shown in SEQ ID NO: 8, wherein the amino acid residue at position 111 is Y or H, and the sequence A variable light chain domain (VL) comprising 1 to 5 conservative amino acid substitutions relative to said VL as shown in identifier number 3, wherein the amino acid residue at position 49 is G or A; and (a), (b The antigen-binding protein of (c), (d), (e) or (f) is not a bispecific binding protein that specifically binds to human CD33 and human CD3, and the CD3 binding site is An antigen binding protein comprising an anti-CD3 variable light chain domain selected from the group consisting of SEQ ID NOs: 1-3 and an anti-CD3 variable heavy chain domain selected from the group consisting of SEQ ID NOs: 6-8.   The antigen-binding protein according to claim 1, wherein the antigen-binding protein is not a bispecific tandem diabody that binds to CD33 and CD3.   The antigen-binding protein according to claim 1 or 2, wherein the antigen-binding protein has at least one other functional domain.   The antigen-binding protein according to claim 3, wherein the at least one other functional domain is another antigen-binding site.   5. The antigen binding protein of claim 4, wherein the other antigen binding site is specific for tumor cells.   6. The antigen binding protein of claim 5, wherein the other antigen binding site is not specific for CD33.   The antigen-binding protein according to any one of claims 1 to 6, wherein the antigen-binding protein is multivalent.   8. The antigen binding protein of claim 7, wherein the antigen binding protein is multispecific.   The antigen-binding protein according to claim 8, wherein the antigen-binding protein is a multimer.   The antigen binding protein is a dimer and has a first polypeptide and a second polypeptide, each of these polypeptides having at least four variable chain domains linked to each other, the antigen binding The antigen-binding protein according to claim 9, wherein the protein has at least one CD3 binding site according to claim 1 and at least one other antigen-binding site specific for the second antigen. 11. The antigen binding protein of claim 10, wherein each polypeptide has at least four variable domains fused together by peptide linkers L1, L2 and L3 in the following order.
(I) VL (CD3)-L1-VH (second antigen)-L2-VL (second antigen)-L3-VH (CD3),
(Ii) VH (CD3)-L1-VL (second antigen)-L2-VH (second antigen)-L3-VL (CD3),
(Iii) VL (second antigen)-L1-VH (CD3)-L2-VL (CD3)-L3-VH (second antigen), or
(Iv) VH (second antigen)-L1-VL (CD3)-L2-VH (CD3)-L3-VL (second antigen)   The antigen-binding protein according to claim 10, wherein the peptide linkers L1, L2, and L3 are composed of about 12 amino acid residues or less.   A polynucleotide encoding the antigen-binding protein according to any one of claims 1 to 12. (I) the antigen-binding protein according to any one of claims 1 to 12, the polynucleotide according to claim 13, or the vector comprising the polynucleotide according to claim 13, and
(Ii) A pharmaceutical composition having a pharmaceutically acceptable carrier. (I) introducing the polynucleotide of claim 13 into a host cell;
(Ii) culturing the host cell under conditions under which the antigen-binding protein is expressed; and
(Iii) The method for producing an antigen-binding protein according to any one of claims 1 to 12, further comprising a step of purifying the expressed antigen-binding protein. The antigen-binding protein according to any one of claims 1 to 12, for use as a medicament .